Estradiol (E2) has a role in learning and memory in mammals such as humans, primates and rats. Following the loss of E2, as occurs during aging, the hippocampus, a brain region important for cognition, undergoes alterations in morphology and synaptic transmission. Specifically, CA1 pyramidal cell dendritic spine density and the magnitude of long-term potentiation (LTP) decrease when the levels of E2 decline. I have shown that E2 transiently increases both spine density and LTP magnitude, with LTP returning to control levels prior to spine density. Whether a relationship exists between these two phenomena has not been determined but I have shown that blocking the estrogen-induced increase in spine density blocks the increase in LTP, which suggests these two phenomena are related. The goal of this study is to determine whether the increase in spine density is required for the increase in LTP magnitude, and if spines are necessary, whether the increase in LTP is due to an increase in NMDAR-only spines, termed silent synapses. Elucidating the contribution of E2 to morphology and synaptic plasticity in hippocampus will provide insight into the mechanism by which E2 regulates cognition with age. [unreadable] [unreadable]